Bo Angelin & Mats Rudling group

Lipid and bile acid metabolism and arteriosclerosis

Cardiovascular diseases are one of the leading causes of death in our country. Elevated cholesterol levels in the blood is one major risk factor for these diseases. Studies have shown that lowering cholesterol in the blood improves the prognosis of cardiovascular disease and prolongs survival.

Our research aim to understand how blood cholesterol is regulated in man by different hormones and by various components in our diet and by inherited familial factors. How this regulation occurs is one key line of the group's research.

Understanding normal physiology often comes from the understanding of the specific mechanisms behind certain diseases and forms the platform to develop novel therapeutic regimens and diagnostic tools. In our work we conduct in vitro, animal and clinical human studies to find and explore the mechanisms regulating blood lipids in humans.

Keywords: Bile acids, thyroid hormone, PCSK9, fibroblast growth factor 19, 21


Bo Angelin, MD, Professor

Bo Angelin is Professor of Clinical Metabolic Research at KI and Consultant at the Department of Endocrinology, Metabolism & Diabetes (Head 1993-2011) at Karolinska University Hospital, where he has also served as Director of Research. His research interest is regulation of lipid and cholesterol metabolism with special emphasis on humans, and how this knowledge can be used for development of new forms of diagnostics and treatments.

Phone: +46-8-585 823 44

Mats Rudling, MD, Professor

Mats Rudling is Professor in Experimental Cardiovascular Medicine. His thesis work was on LDL receptors in tumors at Dept of Pharmacology, KI. His main interest has since then been regulation of plasma LDL cholesterol in man by hormones and diet where LDL receptors are crucial. He did 88-90 post doc work at the laboratory of M Brown and JL Goldstein, Dallas, Texas.

Phone: +46-8-585 869 55, Mobile: +46-739 660 818, Fax: +46-8 711 0710

Lena Persson, M.Sc. PhD

Lena Persson defended her thesis: Studies on PCSK9 in the regulation of cholesterol metabolism, June 2011, and now holds a PhD in Medical Science at Karolinska Institutet. She also holds a master of Medical Science with a major in biomedicine from Uppsala University, Sweden 2006. She is working with several projects involving regulation of cholesterol metabolism by PCSK9.

Sara Straniero, PhD

Had completed her doctoral studies March 2011 under supervision by Prof Bergamini, at the University of Pisa, Italy with her thesis Mechanisms for age-related hypercholesterolemia where she showed that life-long diet enrichment with fish oil (PUFA) counteracts the age dependent increases in blood LDL cholesterol and prolongs the life span of rats.

Ylva Bonde, PhD

Ylva holds a Master of Science degree in Nutrition from the Stockholm University in Sweden 2006. Her PhD project included animal and clinical studies on the effects of thyroid hormone on the regulation of cholesterol and bile acid synthesis.

Johanna Apro, PhD Student

Johanna Apro (formerly Lundberg) holds a Master of Science degree in Nutrition, from the Stockholm University in Sweden (2009). Her PhD projects spans studies on lipoprotein levels in interstitial fluid from type 2 diabetic patients to studies of the regulation of bile acid synthesis.

Beatrice Sjöberg, PhD Student

Beatrice is studying how bile acid synthesis is linked to its putative regulator FGF19 presumable released from the gut and how the level of bile synthesis in humans is linked to plasma triglycerides, blood sugar and to the level of bile acids in circulating blood.

Moumita GhoshMoumita Ghosh, PhD student

Moumita holds a bachelor degree in Pharmacy from India and a master degree in Medical Bio-Sciences (Bio-Medicine) from Linköping University, Sweden. Her PhD projects include cellular, animal and clinical studies regarding regulation of lipoprotein metabolism.

Amani Al-Khaifi, PhD student

Amani Al-Khaifi has a BSc degree in Biotechnology from Sultan Qaboos University (SQU) and MSc in Biomedicine from KI. She works on several projects concerning the role of the novel growth factor FGF19 on cholesterol and bile acids metabolism in normal and hyperlipidemic patients.

Daniela StrodthoffDaniela Strodthoff, Post doc

Daniela Strodthoff studied biology in Kiel, Germany. She did her PhD in the Department of Medicine, Solna, Karolinska Institutet. During her PhD she worked on inflammation and lipid metabolism in atherosclerosis and obesity. She is now interested in investigating the role and function of genes involved in lipid and bile acid metabolism.

Amit Laskar, Post doc

Amit Laskar started with a bachelors degree in Pharmacy from India, and then continued with a Masters degree in Biomedicine in Linköping University Sweden. He achieved his Ph.D in Medicine from Linköping University Sweden, 2013, where he focused on understanding the molecular mechanisms including abnormal lipid metabolism underlying pathophysiology of atherosclerosis and usage of MRI contrast agents as a diagnostic approach. His focus now is to further understand the role of lipid metabolism in conjunction with bile acid metabolism and underlying genes in the development of chronic metabolic and inflammatory conditions as Diabetes and Atherosclerosis. 

Ingela Arvidsson, Biomedical analyst

Ingela Arvidsson is a biomedical analyst with expertise in the groups advanced analytical procedures employed by the group including mass spectrometry, gas chromatography, HPLC, FPLC, ultracentrifugation

Lisbeth Benthin, Medical laboratory technologist


Past members

Tomas Lundåsen, Cecilia Gälman, Manuela Matasconi, Paolo Parini


The projects aim to understand key gate keepers in bile acid and cholesterol metabolism.

Large amounts of cholesterol is made in the liver by HMGCoA reductase. Cholesterol is used for buildup and export of triglyceride-rich VLDL particles or excreted into bile as such or after degradation into bile acids. Cholesterol is returned to liver in LDL particles binding to LDL receptors. HDL collect cholesterol from peripheral tissues that is returned to liver for excretion (reverse cholesterol transport). HDL bind to another liver receptor, SR-BI.

Hormonal and dietary regulation of PCSK9

The number of hepatic LDL receptors determines the LDL level in blood. The protein PCSK9 (proprotein convertase subtilisin / Kexin type 9) reduces LDL receptors resulting in increased LDL cholesterol in blood. The best cholesterol lowering drugs are statins, that increase LDL receptors.

One side effect of statins is that they increase PCSK9 which reduces the effects of statins. PCSK9 is a hot drug target, and the reduction of PCSK9 reduces LDL cholesterol. We have shown that estrogen, glucagon, insulin, growth hormone and thyroid hormone regulate PCSK9 in vivo. We have also discovered that PCSK9 is regulated during the diurnal phases, by fasting, and by diets rich in unsaturated fatty acids placing our group in the front edge here. These studies are conducted by L Persson.

Are the lipoproteins in lymph increased in diabetes type 2?

In diabetes type 2 arteriosclerosis is common in spite of modest LDL levels and indirect data have shown that the transvascular transport of LDL is increased in such patients. The question now is if the relative level of lipoproteins is increased in lymph in diabetes type 2 compared with healthy subjects. Blistering of the skin is created by vacuum and lipoproteins in the blister fluid are determined by FPLC in patients and healthy controls. The project is conducted by J Apro .

Why does cholesterol in blood increase with aging?

When people age LDL cholesterol in blood increase of unclear reasons. We try to get insight in the mechanisms that are responsible for this in humans and in animals.

Discovering genetic hyperlipidemias from extreme phenotypes combined with whole genome sequencing

Patients with familial hypercholesterolemia (FH), familial combined hyperlipidemia (FCHL) and familial hypertriglyceridemia (FHTG) and family members have been collected and their genomes are now sequenced to identify the disease cause in collaboration with Prof Juha Kere. This project has a high expansion potential.

Hormonal and dietary regulation of bile acid synthesis

Since bile acid metabolism is so important for cholesterol metabolism we study how LDL lowering diets such as PUFA enriched diets and hormonal states such as conditions with high estrogens and thyroid hormone alter bile acid and cholesterol metabolism to understand the mechanisms how LDL cholesterol is reduced.

Metabolic regulation with bile acids and their possible mediators

In recent years it has become clear that bile acids after binding to specific receptors modulate cholesterol, triglyceride, and sugar metabolism. Some novel metabolic regulators exerting effects here are eg the fibroblast growth factors FGF19 and FGF21. In our studies we attempt to elucidate if these factors have any effects in humans as has been outlined in rodents.

The projects are supported by Swedish Research Council, the Stockholm City Council (ALF) and the Cardiovascular Program, Karolinska Institutet/Stockholm City Council and The Heart-Lung Foundation.

Selected publications

Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial.
Bjermo H, Iggman D, Kullberg J, Dahlman I, Johansson L, Persson L, et al
Am. J. Clin. Nutr. 2012 May;95(5):1003-12

Endogenous estrogens lower plasma PCSK9 and LDL cholesterol but not Lp(a) or bile acid synthesis in women.
Persson L, Henriksson P, Westerlund E, Hovatta O, Angelin B, Rudling M
Arterioscler. Thromb. Vasc. Biol. 2012 Mar;32(3):810-4

Pronounced variation in bile acid synthesis in humans is related to gender, hypertriglyceridaemia and circulating levels of fibroblast growth factor 19.
Gälman C, Angelin B, Rudling M
J. Intern. Med. 2011 Dec;270(6):580-8

Lipid lowering with thyroid hormone and thyromimetics.
Angelin B, Rudling M
Curr. Opin. Lipidol. 2010 Dec;21(6):499-506

Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans.
Persson L, Cao G, Ståhle L, Sjöberg B, Troutt J, Konrad R, et al
Arterioscler. Thromb. Vasc. Biol. 2010 Dec;30(12):2666-72

The liver-selective thyromimetic T-0681 influences reverse cholesterol transport and atherosclerosis development in mice.
Tancevski I, Demetz E, Eller P, Duwensee K, Hoefer J, Heim C, et al
PLoS ONE 2010 Jan;5(1):e8722

Intranasal immunization with an apolipoprotein B-100 fusion protein induces antigen-specific regulatory T cells and reduces atherosclerosis.
Klingenberg R, Lebens M, Hermansson A, Fredrikson G, Strodthoff D, Rudling M, et al
Arterioscler. Thromb. Vasc. Biol. 2010 May;30(5):946-52

Importance of proprotein convertase subtilisin/kexin type 9 in the hormonal and dietary regulation of rat liver low-density lipoprotein receptors.
Persson L, Gälman C, Angelin B, Rudling M
Endocrinology 2009 Mar;150(3):1140-6

The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARalpha activation in man.
Gälman C, Lundåsen T, Kharitonenkov A, Bina H, Eriksson M, Hafström I, et al
Cell Metab. 2008 Aug;8(2):169-74

Dramatically increased intestinal absorption of cholesterol following hypophysectomy is normalized by thyroid hormone.
Gälman C, Bonde Y, Matasconi M, Angelin B, Rudling M
Gastroenterology 2008 Apr;134(4):1127-36

The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans.
Berkenstam A, Kristensen J, Mellström K, Carlsson B, Malm J, Rehnmark S, et al
Proc. Natl. Acad. Sci. U.S.A. 2008 Jan;105(2):663-7

PPARalpha is a key regulator of hepatic FGF21.
Lundåsen T, Hunt M, Nilsson L, Sanyal S, Angelin B, Alexson S, et al
Biochem. Biophys. Res. Commun. 2007 Aug;360(2):437-40

Age-induced hypercholesterolemia in the rat relates to reduced elimination but not increased intestinal absorption of cholesterol.
Gälman C, Matasconi M, Persson L, Parini P, Angelin B, Rudling M
Am. J. Physiol. Endocrinol. Metab. 2007 Sep;293(3):E737-42

Circulating intestinal fibroblast growth factor 19 has a pronounced diurnal variation and modulates hepatic bile acid synthesis in man.
Lundåsen T, Gälman C, Angelin B, Rudling M
J. Intern. Med. 2006 Dec;260(6):530-6